Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I

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  • dc.contributor.author Rodríguez-Nuevo, Aida
  • dc.contributor.author Torres-Sanchez, Ariadna
  • dc.contributor.author Duran, Juan M.
  • dc.contributor.author De Guirior, Cristian
  • dc.contributor.author Martínez-Zamora, Maria Angeles
  • dc.contributor.author Böke, Elvan
  • dc.date.accessioned 2022-11-04T07:45:40Z
  • dc.date.available 2022-11-04T07:45:40Z
  • dc.date.issued 2022
  • dc.description.abstract Oocytes form before birth and remain viable for several decades before fertilization1. Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age2. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival3-5. Yet, how healthy oocytes balance essential mitochondrial activity with the production of ROS is unknown. Here we show that oocytes evade ROS by remodelling the mitochondrial electron transport chain through elimination of complex I. Combining live-cell imaging and proteomics in human and Xenopus oocytes, we find that early oocytes exhibit greatly reduced levels of complex I. This is accompanied by a highly active mitochondrial unfolded protein response, which is indicative of an imbalanced electron transport chain. Biochemical and functional assays confirm that complex I is neither assembled nor active in early oocytes. Thus, we report a physiological cell type without complex I in animals. Our findings also clarify why patients with complex-I-related hereditary mitochondrial diseases do not experience subfertility. Complex I suppression represents an evolutionarily conserved strategy that allows longevity while maintaining biological activity in long-lived oocytes.
  • dc.description.sponsorship The graphical representation in Extended Data Fig. 3a was adapted from the TMT Labeling Protocol, by BioRender.com (2022), retrieved from https://app.biorender.com/biorender-templates. E.B. acknowledges support from MINECO’s Proyectos de Excelencia (BFU2017-89373-P), and a European Research Council Starting Grant (DORMANTOOCYTE – 759107). We also acknowledge the support of the Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Rodríguez-Nuevo A, Torres-Sanchez A, Duran JM, De Guirior C, Martínez-Zamora MA, Böke E. Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I. Nature. 2022 Jul;607(7920):756-61. DOI: 10.1038/s41586-022-04979-5
  • dc.identifier.doi http://dx.doi.org/10.1038/s41586-022-04979-5
  • dc.identifier.issn 0028-0836
  • dc.identifier.uri http://hdl.handle.net/10230/54692
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature. 2022 Jul;607(7920):756-61
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89373-P
  • dc.rights © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Infertility
  • dc.subject.keyword Mitochondria
  • dc.subject.keyword Oogenesis
  • dc.title Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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